在哺乳动物细胞中,MAD2的哈普洛缺陷会导致过早的亚纳相和染色体不稳定
L S Michel1, V Liberal, A Chatterjee
1Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Nature
|February 24, 2001
概括
线粒体检查点蛋白 Mad2 (线粒体停止缺陷2) 的部分损失导致染色体不稳定,并促进瘤形成. 这项研究揭示了微妙的检查点缺陷可以驱动瘤发生.
科学领域:
- 细胞生物学 细胞生物学
- 遗传学 是一个遗传学.
- 癌症研究 癌症研究
背景情况:
- 线性检查点通过延迟细胞分裂,确保精确的染色体分离,直到所有染色体都附着在线索上.
- 由于广泛的染色体错误分离,线粒检查点功能的完全丧失导致胚胎死亡.
- 线粒体检查点控制中的部分缺陷对染色体稳定性和生物体活力的后果尚不清楚.
研究的目的:
- 为了研究线粒体检查点蛋白 Mad2 (线粒体停滞缺陷2) 的部分损失对细胞和生物忠实性的影响.
- 确定线粒检查点控制中的微妙缺陷是否有助于染色体不稳定性和瘤发生.
主要方法:
- 在人类癌细胞和小鼠初级胚胎纤维细胞中删除一个MAD2等位基因.
- 在螺旋抑制剂治疗下过早分离姐妹染色体的分析.
- 在没有螺旋剂的情况下评估染色体错误分离率.
- 长期观察Mad2+/-小鼠的瘤发育情况.
主要成果:
- 删除一个MAD2等位基因导致人类和小鼠细胞中缺陷的线粒检查点.
- 检查点缺陷细胞表现出过早的姐妹染色体分离和增加的染色体错误分离.
- 经过长时间的潜伏期,Mad2+/-小鼠在高频率下发展出肺瘤.
结论:
- 线粒检查点蛋白 Mad2 的部分损失损害了染色体的稳定性.
- 线粒体检查点的缺陷,即使是部分缺陷,也与促进瘤发生有关.
- 这项研究强调了强大的线粒体检查点功能在预防癌症发展中的关键作用.
相关概念视频
01:57Meiosis II
169.4K
Meiosis II is the second and final stage of meiosis. It relies on the haploid cells produced during meiosis I, each of which contain only 23 chromosomes—one from each homologous initial pair. Importantly, each chromosome in these cells is composed of two joined copies, and when these cells enter meiosis II, the goal is to separate such sister chromatids using the same microtubule-based network employed in other division processes. The result of meiosis II is two haploid cells, each...
169.4K
01:36Mismatch Repair
38.1K
Overview
38.1K
01:29Nondisjunction
68.0K
During meiosis, chromosomes occasionally separate improperly. This occurs due to failure of homologous chromosome separation during meiosis I or failed sister chromatid separation during meiosis II. In some species, notably plants, nondisjunction can result in an organism with an entire additional set of chromosomes, which is called polyploidy. In humans, nondisjunction can occur during male or female gametogenesis and the resulting gametes possess one too many or one too few chromosomes.
68.0K
02:23Abnormal Proliferation
4.0K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.0K
02:02Meiosis II
32.7K
Meiosis II entails cell division and segregation of the sister chromatids, resulting in the production of four unique haploid gametes. The steps for meiosis II are similar to mitosis, except that meiosis II occurs in haploid cells, whereas mitosis occurs in diploid cells.
The timing and cell division patterns of meiosis differ between males and females. In male meiosis, the centrosomes are part of the formation of the meiotic spindle. However, in oocytes, including that of humans, Drosophila,...
The timing and cell division patterns of meiosis differ between males and females. In male meiosis, the centrosomes are part of the formation of the meiotic spindle. However, in oocytes, including that of humans, Drosophila,...
32.7K
01:20Mismatch Repair
5.4K
Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
5.4K